Blocking Cancer With Combinations of Supplements and Off-Label Drugs

Targeting cancer cell metabolism, growth signaling pathways and enhancing anti-cancer immunity are among the hottest topics being explored in oncology, today. It has become increasingly clear that many natural compounds, supplements and FDA-approved medications possess these anticancer properties, and look quite promising in both preclinical and clinical studies. In fact, over 200 non-cancer drugs have shown some evidence of anticancer effects. Of these, 50% are supported by relevant human data and 16% are supported by data from at least one positive clinical trial. Some of these drugs include: mebendazole, cimetidine, nitroglycerin, diclofenac, itraconazole, clarithromycin, metformin, aspirin and hydroxychloroquine – all common, generic drugs with excellent safety records and a wide range of data sources showing potent anticancer effects.

Instead of waiting for years for new drugs that exploit these anticancer mechanisms to be developed, studied for safety and efficacy and approved by the FDA, patients are taking matters into their own hands and treating themselves with thoughtful combinations of these agents to hopefully improve their cancer outcomes. This is often called “repurposing” when existing and well-characterized non-cancer drugs are used as treatments for cancer – either as additions to existing drug protocols or in novel combinations with multiple repurposed drugs.

Drug repurposing of inexpensive generics has been gaining interest over the years for two major reasons: 1) Repurposed, generic cancer drugs have the potential to significantly reduce the financial burden on patients and health care systems from high-cost pharmaceuticals. 2) The time to bring repurposed, non-cancer drugs through the clinical trials and FDA approval process (which typically takes 10+ years) should be much faster than with newer cancer compounds, since these are well-known and well-characterized drugs. Much of the hard work of conducting the preliminary studies (i.e. pharmacodynamics, pharmacokinetics, bioavailability, toxicities, established protocols and dosing) has already been done.

What are “off-label” drugs? These are prescription drugs that are approved by the Food and Drug Administration for specific uses to treat specific conditions or diseases. This can mean that the drug is:

Used for a different disease or medical condition

Given in a different way (such as by a different route)

Given in a different dose than in the approved label

Physicians may prescribe a drug for a use that’s not described in the approved labeling if it seems reasonable or appropriate to them. This is what’s called “off-label use.” For example, it is not uncommon for physicians to prescribe low doses of beta blocker drugs to help people overcome jitters before public speaking. Beta blockers are not formally approved for this use. The FDA advises doctors in such circumstances that “they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.”

Why are drugs used “off-label”? Older, generic (non-brand name) medicines are the ones most often used off label. New uses for these drugs may have been found and there’s often medical evidence from research studies to support the new use. But it’s often too costly for the makers of the drugs to put them through the formal, lengthy, and expensive process required by the FDA to officially approve the drug for new uses. Many patients, especially those with diagnoses of aggressive or advanced malignancies, express that they do not have the luxury of waiting for well-designed clinical trials to prove/disprove the effectiveness of a compound that looks very promising in preclinical, pilot clinical and retrospective studies.

Barriers to “off-label” drug use: The biggest problem is getting insurance plans to reimburse for off-label drug use. Many insurance companies will not pay for a drug that’s used in a way that’s not listed in the approved drug label. They do this on the grounds that its use is “experimental” or “investigational.” Another problem is that off-label drug use often does not reflect “standard of care” treatment. This could raise concerns about the legal risk to the health care provider should a patient have an unwanted or bad outcome from the treatment. Finally, there is also a lack of information about how to best use the drug other than for what it was approved. Lack of information on off-label drug use and outcomes may put patients at a higher risk for medication errors, side effects, and unwanted drug reactions. It’s important that the patient and doctor talk about the possible risks of using the drug and weigh them against the possible benefits.

Anticancer supplements: There are thousands of plant-derived and nutrient compounds that have been shown in preclinical and clinical studies to exhibit similar pharmacologic properties with many of the “off-label” non-cancer drugs. Unfortunately, the majority of these compounds have not been studied with similar rigor compared with FDA-approved pharmaceuticals and the lack of standardization in dosing, manufacturing and other quality and safety concerns adds more questions than answers on their potential use in cancer treatment protocols. Regardless, the use of anticancer supplements by patients is prolific.

Use of multiple compounds: Due to the complexity of cancer growth and metabolism, development of resistance and an individual’s physiology (i.e. immune system, tumor microenvironment, etc.), many conventional oncology treatments employ combination therapies to target these variables. This is the same rationale for the use of multiple “off-label” drugs and supplements, which are thoughtfully selected based on their purported effects on inhibiting important drivers of cancer growth and enhancing anticancer systems in the host.

The figure, below, (McLelland ‘Metro Map’, from the book: How To Starve Cancer, by Jane McLelland. Used with the author’s permission) serves as a great example of how one might use an evidence-informed approach to combine various “off-label” non-cancer drugs and supplements to simultaneously target key metabolic pathways used by cancer cells for growth and survival. Blocking one metabolic pathway (i.e. glucose metabolism) at a time is not effective, as most cancers are able to use other energy sources for their survival (i.e. fatty acids, ketones, amino acids.)

Block Tumor Cell Metabolic Pathways with Off-Label Non-Cancer Drugs and Supplements (Source: How To Starve Cancer, by Jane McLelland. Used with the author’s permission.)

What are the most effective drugs for your cancer? I wish I could tell you that there is a non-invasive, inexpensive and simple way to figure this out. Unfortunately, there isn’t. What I typically see the vast majority of patients doing is to take different compounds and 1) hope they don’t develop side effects and 2) see a favorable response to treatment on imaging, clinical exam or follow-up. Eventually, we will have assays (such as the EVA-PCD assay) that will be able to test hundreds of compounds on a sample of your cancer to see which combinations work the best.

Warning: As with any pharmaceutical or supplement, there are concerns about potential side effects, toxicity and harmful interactions between these compounds and other conventional treatments. It is essential that patients understand these issues and discuss their interest in using these compounds with their oncology providers before starting them.

List of some of the more popular anticancer compounds:

Dosing information derived from the design and methods sections of published and unpublished clinical studies (main source: ClinicalTrials.Gov)

Tetrathiomolybdate “TM” (Induction phase: 40 mg 3 x/day with meals and an additional 60 mg at bedtime. Goal of induction phase is to decrease ceruloplasmin level to 5-15 mg/dL. Once this is achieved, the maintenance phase will begin: 40 mg 2 x/day with meals and an additional 20 mg at bedtime.)

If you are interested in learning more about these drugs and compounds or have questions about your cancer care and want a more integrative/functional medicine-based approach, I offer 1-on-1, 60 minute counseling sessions. Learn more here.

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About Brian D. Lawenda, M.D.

I am an integrative oncologist. I trained at Massachusetts General Hospital (Harvard Medical School) in radiation oncology and through Stanford-UCLA (Helms Medical Institute) in medical acupuncture. I am the founder of IntegrativeOncology-Essentials.